1INY

A SIALIC ACID DERIVED PHOSPHONATE ANALOG INHIBITS DIFFERENT STRAINS OF INFLUENZA VIRUS NEURAMINIDASE WITH DIFFERENT EFFICIENCIES

1INY の概要

• エントリーDOI: 10.2210/pdb1iny/pdb
• 分子名称: INFLUENZA A SUBTYPE N9 NEURAMINIDASE, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: hydrolase, o-glycosyl, neuraminidase, sialidase
• 由来する生物種: Influenza A virus
• 細胞内の位置: Virion membrane (By similarity): P03472
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 45796.69

構造登録者

White, C.L.,Janakiraman, M.N.,Laver, W.G.,Philippon, C.,Vasella, A.,Air, G.M.,Luo, M. (登録日: 1994-09-26, 公開日: 1995-02-07, 最終更新日: 2024-10-23)

主引用文献

White, C.L.,Janakiraman, M.N.,Laver, W.G.,Philippon, C.,Vasella, A.,Air, G.M.,Luo, M.
A sialic acid-derived phosphonate analog inhibits different strains of influenza virus neuraminidase with different efficiencies.
J.Mol.Biol., 245:623-634, 1995

PubMed Abstract: A phosphonate analog of N-acetyl neuraminic acid (PANA) has been designed as a potential neuraminidase (NA) inhibitor and synthesized as both the alpha (ePANA) and beta (aPANA) anomers. Inhibition of type A (N2) and type B NA activity by ePANA was approximately a 100-fold better than by sialic acid, but inhibition of type A (N9) NA was only ten-fold better than by sialic acid. The aPANA compound was not a strong inhibitor for any of the NA strains tested. The crystal structures at 2.4 A resolution of ePANA complexed to type A (N2) NA, type A (N9) NA and type B NA and aPANA complexed to type A (N2) NA showed that neither of the PANA compounds distorted the NA active site upon binding. No significant differences in the NA-ePANA complex structures were found to explain the anomalous inhibition of N9 neuraminidase by ePANA. We put forward the hypothesis that an increase in the ePANA inhibition compared to that caused by sialic acid is due to (1) a stronger electrostatic interaction between the inhibitor phosphonyl group and the active site arginine pocket and (2) a lower distortion energy requirement for binding of ePANA.

PubMed: 7844831
DOI: 10.1006/jmbi.1994.0051

実験手法

X-RAY DIFFRACTION (2.4 Å)